POS0485 PLATELET-DERIVED MICROPARTICLES IN SYSTEMIC SCLEROSIS: POTENTIAL NEW PROFIBROTIC BIOMARKER?
Authors: S. Maximiano de Oliveira, I. L. De Azevedo Teixeira, C. Nunes França, M. C. De Oliveira Izar, C. Kayser
Journal: Annals of the Rheumatic Diseases (2022)

Background Systemic sclerosis (SSc), the most lethal autoimmune rheumatic disorder, is characterized by vascular damage, immune dysregulation and progressive tissue fibrosis [1]. Microparticles (MP) are membrane-derived vesicles released from cells undergoing activation or apoptosis, that participate in regulation of inflammatory responses, homeostasis and vascular function [2]. Prior studies have reported elevated plasma levels of MP in SSc [3,4], but its association with clinical SSc features and its role in the disease pathogenesis has still not been completely elucidated. Objectives We aimed to compare serum levels of platelets-derived microparticles (PMP), endothelial cells-derived microparticles (EMP), and monocytes-derived microparticles (MMP) between SSc patients and healthy controls. Also, we aimed to evaluate the association of MP and SSc clinical features. Methods In this cross-sectional study, 70 SSc patients and 35 age- and sex-matched healthy controls were recruited. After staining with fluorescent cell-specific monoclonal antibodies (PMP CD42 + /31 + , EMP CD105 + , and MMP CD14 + ), plasma MP were quantified by flow cytometry. Clinical and nailfold capillaroscopy data from patients were obtained. All of them fulfilled the 2013 ACR/EULAR classification criteria for SSc. Results Clinical features of studied population are shown on Table 1. Serum MP levels were significantly increased in SSc patients compared to healthy controls (mean ± SD): 79.2% ± 17.3% vs 71.0% ± 19.8% for PMP ( p = 0.033); 43.5% ± 8.7% vs 37.8% ± 10.4% for EMP ( p = 0.004); and 3.5% ± 1.3% vs 1.1% ± 0.5% for MMP ( p &lt; 0.001) (Figure 1). We observed significantly higher PMP levels in patients with positive anti-topoisomerase-I antibodies compared to those with negative anti-topoisomerase-I antibodies ( p = 0.030) and in patients with disease duration &gt; 3 years compared to patients with disease duration ≤ 3 years ( p = 0.038). Table 1. Demographic and clinical data of studied population Variable SSc (n=70) Healthy controls (n=35) p Female/Male 63 (90) / 7 (10) 31 (88.5) / 4 (11.4) 0.68 Age, yr. 48.9 ± 13.4 47.6 ± 14.0 0.63 Limited SSc/Diffuse SSc 44 (62.9) / 26 (37.1) -- -- Disease duration, yr. 6.4 ± 4.0 -- -- Modified Rodnan skin score 6.5 ± 9.6 -- -- Active digital ulcers 15 (21.4) -- -- FVC, ( n=63 ) 80.9 ± 17.4 -- -- ILD 38 (54.3) -- -- PAH 4 (5.7) -- -- Esophageal dyskinesia 42 (60) -- -- Cardiac involvement 8 (11.4) -- -- Autoantibodies Anticentromere 13 (18.6) -- -- Anti-topoisomerase-I 13 (18.6) -- -- Nailfold capillaroscopy, (n=61 ) SD Early 23 (37.7) -- -- SD Active 15 (24.5) -- -- SD Late 23 (37.7) Calcium channel blockers in use 49 (70) -- -- Phosphodiesterase-5 inhibitors in use 9 (12.9) -- -- Immunosuppressors in use Glucocorticoids 8 (11.4) -- -- Cyclophosphamide 3 (4.3) -- -- Mycophenolate 15 (21.4) -- -- Azathioprine 3 (4.3) -- -- Rituximab 1 (1.4) -- -- Methotrexate 12 (17.1) -- -- Data are mean ± SD or n (%) unless otherwise stated. FVC: forced vital capacity; ILD: interstitial lung disease; PAH; pulmonary arterial hypertension. Figure 1. MP plasma levels in SSc patients vs healthy controls Conclusion Serum levels of PMP, EMP and MMP are elevated in scleroderma patients, thus indicating a possible role of these agents in SSc pathogenic mechanisms. The higher plasma titles of PMP observed in patients with longer disease duration and presence of anti-topoisomerase-I, a well-established factor of worse prognosis in SSc, might suggest a profibrotic function for this new potential biomarker. References [1]Saketkoo LA et al. Best Pract Res Clin Rheumatol , 2021;35:101707. [2]Beyer C, Pisetsky DS. Nat Rev Rheumatol , 2010;6:21-9. [3]Dunne JV et al. Curr Rheumatol Rev , 2013;9:279-300. [4]Čolić J et al. J Scleroderma Relat Disord , 2019;5:1-15. Acknowledgements We appreciate the financial support given by FAPESP (grant 2018/15216-2) and FAPE-SBR. Disclosure of Interests None declared.